TRIM44

Chr 11AD

tripartite motif containing 44

Also known as: AN3, DIPB, HSA249128, MC7

This protein contains RING and B-box zinc-binding domains and negatively regulates PAX6 expression, which is critical for eye development. Mutations cause aniridia 3, characterized by absence or underdevelopment of the iris, with autosomal dominant inheritance. The gene shows moderate constraint to loss-of-function variants (LOEUF 0.659).

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Aniridia 3MIM #617142
AD
0
Active trials
15
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.66
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryTRIM44
🧬
Gene-Disease Validity (ClinGen)
aniridia 3 · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.054
Z-score 2.54
OE 0.31 (0.160.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.07Z-score
OE missense 0.78 (0.680.90)
150 obs / 191.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.160.66)
00.351.4
Missense OE0.78 (0.680.90)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 5 / 15.9Missense obs/exp: 150 / 191.7Syn Z: 0.88
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTRIM44-related aniridiaOTHERAD
DN
0.74top 25%
GOF
0.7125th %ile
LOF
0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRIM44 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →